A facile one-pot procedure for the transformation of acetonides into diacetates catalyzed with Bi(OTf)3·xH2O

Article abstract of DOI:10.1016/j.tetlet.2008.02.163

The transformation of acetonides into the corresponding diacetates is often required in the synthetic chemistry. An efficient procedure for direct conversion of acetonides into diacetates in the presence of Bi(OTf)₃·xH₂O under mild c

Full text of DOI:10.1016/j.tetlet.2008.02.163

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 2714–2718
A facile one-pot procedure for the transformation of
acetonides into diacetates catalyzed with Bi(OTf)3ꢀxH2O
Qin-Pei Wu a,b,*, Ming-Xin Zhou a, Xiao-Dong Xi a, Di Song a, Yuan Wang b,
Hai-Xia Liu a, Yun-Zheng Li a, Qing-Shan Zhang a,*
a School of Chemical Engineering and Environment, Beijing Institute of Technology, Beijing 100081, PR China
b School of Life Science and Technology, Beijing Institute of Technology, Beijing 100081, PR China
Received 31 October 2007; revised 27 February 2008; accepted 29 February 2008
Available online 4 March 2008
Abstract
The transformation of acetonides into the corresponding diacetates is often required in the synthetic chemistry. An efficient procedure
for direct conversion of acetonides into diacetates in the presence of Bi(OTf)3ꢀxH2O under mild conditions has been developed. Primary
hydroxyl-acetonides could be selectively transformed into diacetates in the presence of anomeric acetonides and the anomeric acetonides
could be tunably converted into 2-acetoxyisopropyl or diacetate groups.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Acetal; Acetate; Acetonide; Homogeneous catalysis; Protecting groups
1. Introduction
acetonides and acetates are complementary in stability
and sensitivity under acid- and base-conditions. Practi-
cally, the transformation of acetonides into diacetates is
frequently encountered and employed in synthetic chemis-
try, particularly, in the synthesis of carbohydrates and
nucleosides.6
The acetonide is one of the most frequently used pro-
tecting groups in synthetic chemistry because they are
readily introduced and removed, as well as they are con-
siderably stable under most reaction conditions.1 As an
efficient protecting group for vicinal diols, isopropylidene
group has also been extensively employed in carbohydrate
chemistry,2 nucleoside3 and polyhydroxy compound
chemistry.4 This group is acid and Lewis acid sensitive
while it survives under strongly basic conditions, for
example, alkyl lithium reagents, metal hydride reduction
and catalytic hydrogenation reactions. On the other hand,
acetates are also frequently employed to mask hydroxy
groups and with typical characteristics of base-lability
and acid-stability.5 Therefore, as protecting groups, both
To the best of our knowledge, the methods documented
for accomplishing this transformation involved two steps:
first, the removal of isopropylidene groups and subse-
quently, acetylation with acetic anhydride. For example,
treatment with 80% AcOH first and followed by Ac2O–pyr-
idine;7 treatment with 6 M H2SO4 in dioxane at 100 °C for
2 h and then with AcOH, Ac2O–H2SO4 at rt for 10 h;8 or
TFA first and followed by Ac2O–pyridine.9 Huang and
Bobek10 reported a method to convert 1,2-isopropylidene
of glucofuranose derivatives into corresponding 1-acet-
oxy-2-benzoyloxy derivatives via the cleavage of isopropyl-
idene acetal with iodine–methanol and subsequent
benzoylation and acetylation, respectively. Herein, we wish
to report an efficient method for the direct conversion of
acetonides into corresponding diacetates.
*
Corresponding authors. Fax: +8610 6891 2917 (Q.-P.W.).
E-mail addresses: qpwu@bit.edu.cn (Q.-P. Wu), zhangqsh@bit.edu.cn
(Q.-S. Zhang).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.02.163

Q.-P. Wu et al. / Tetrahedron Letters 49 (2008) 2714–2718
2715
conditions as mentioned above to be expected to give the
corresponding acetates. As the matter of fact, these
isopropylidene groups were maintained intact and only
hydroxyl groups were acetylized to give diacetate 9 and
triacetate 2 (Table 1, entries g and h), respectively.
Other Lewis acids were employed as substitutes for
Bi(OTf)3ꢀxH2O to be expected to induce direct transforma-
tion. However, no satisfactory result was obtained under
various conditions. For instances, BiCl3 and InCl3 led to
no product at all; 13 was converted into an unexpected
product 14 with FeCl3 and AlCl3 as catalysts and BF3
etherate led to the expected products in neat Ac2O with
moderate yields.
Ac2O (3 eq),
O
O
AcO
AcO
O
O
HO
AcO
O
Bi(OTf)3 xH2O(5mol %)
CH2Cl2, rt, 89%
O
O
O
1
2
2. Results and discussion
In the course of our continuous research in the synthesis
of nucleosides, the treatment of glucose diacetonide 1 with
acetic anhydride at room temperature in the presence of
Bi(OTf)3ꢀxH2O (5 mol %) in CH2Cl2 generated the triacetyl
product 2 in 89% yield. Furthermore, Bi(OTf)3 has been
OAc
OAc
OAc
AcO
AcO
AcO
OAc
14
BzO
BzO
BzO
BzO
O
Bi(OTf)3 xH2O(5 mol %)
O
O
OAc
OAc
Ac2O (3 eq), CH2Cl2
rt, 91%
O
O
15
16
BzO
O
BzO
BzO
O
OAc
OMe
OAc
BzO
O
OH
17
18
widely employed in organic synthesis recently.11 This inter-
esting result prompted us to examine the scope of this
direct transformation protocol. More sugar acetonides
were prepared and treated with Ac2O (3.0 equiv) under
similar reaction conditions. As for all glucose diacetonide
1, 3, 5 and 6 and xylose derivatives 8, it can be seen as
shown in Table 1, the primary hydroxy acetonides were
selectively converted into relative diacetates with excellent
yields in the presence of the anomeric acetonide under this
one–pot reaction conditions (Table 1, entries a–e). In addi-
tion, the anomeric isopropylidene groups could not be
substituted by acetyl groups even though more Ac2O was
added and reaction time was extended, which showed
how selective this reaction was under these mild conditions.
As anticipated, mannose diacetonide 10 was selectively
transformed into triacetates 11 in 91% yield. The anomeric
benzoate was also displaced by acetate group (Table 1,
entry f) with the inversed configuration of 1-C. However,
direct transformation of the anomeric acetonides into
diacetates is quite valuable in the synthesis of nucleosides
in view of the common synthetic methods for nucleosides.12
Therefore, monoacetonide sugar derivatives 12 and 13
were treated with Ac2O (10 equiv) under the same reaction
Accordingly, 3,5-dibenzoyl acetonide 15 was subjected
to this one-pot procedure. Undesired product 16 was
obtained as an oil in 91% isolated yield, in which the iso-
propylidene group was partially transformed. The mole-
cular structure was characterized by 1H NMR, 13C
NMR and MS (ESI) spectra. In order to further elucidate
the position of the 2-acetoxyisopropyl group, 16 was trea-
ted with absolute methanol in the presence of
Bi(OTf)3ꢀxH2O (10 mol %) at room temperature to give
17 in 80% yield rather than the desired product with the
loss of 2-acetoxyisopropyl group. Besides the signals for
the isopropylidene group, the resonance signal of anomer-
ic proton (17, H-1) appeared upfield (d 5.70) in contrast
to the corresponding resonance signal (d 6.33, H-1) for
1
compound 16 in H NMR spectra. In addition, neither
16 nor 17 was an a- and b-mixture but a pure isomer.
To the best of our knowledge, this half cleaved anomeric
acetonide 16 has never been documented and it is valu-
able in synthetic chemistry due to its lability to release
hydroxyl group under mild conditions. In the solution
of acetonitrile–H2O with BiCl3 (10 mol %) as the catalyst
at room temperature, the 2-acetoxyisopropyl group in 16
was cleaved to form 18 in 75% yield, in which the –OH

2716
Q.-P. Wu et al. / Tetrahedron Letters 49 (2008) 2714–2718
Table 1
(ESI) spectra. Moreover, the stereoselective products
would be quite useful for the stereoselective synthesis of
nucleosides.
Selective transformation of acetonides into diacetates with Bi(OTf)3ꢀxH2O
(5 mol %) at rt
Entry Substrate
Producta
Time Yieldb
Since acyclic acetyloxyacetal might be more reactive
than cyclic acetal, it would be possible to convert com-
pound 26 into pentaacetyl glucofuranoside 29. Therefore,
a solution of 3,5,6-tri-O-acetyl-1,2-O-isopropylidene-a-D-
glucofuranose 2, Ac2O (3 equiv) and Bi(OTf)3ꢀxH2O
(5 mol %) in dichloromethane was heated under reflux.
Compound 26, however, was still obtained as the main
product with trace amounts of the expected product 29.
Finally, 29 (85%) was obtained in reflux CH2Cl2 solution
with increasing amount of catalyst, Bi(OTf)3ꢀxH2O, by
15 mol % (Table 3, entry a), and 26 was also observed on
TLC plate as an intermediate in this process. Additionally,
29 is an anomeric mixture rather than a single product.
Under this one-pot reaction conditions, a number of ano-
meric acetonides, 4, 7, 9 and 15 (Table 3, entries b–e), were
also directly converted into corresponding diacetates in
good yields.
In conclusion, we have established a useful procedure
for the direct transformation of the acetonides into the cor-
responding acetates efficiently under mild conditions, and
this protocol has some advantages: excellent selectivity
between the transformation of the primary hydroxyl-aceto-
nides and anomeric acetonides; tunable transformation of
anomeric acetonides into relative diacetates or acyclic
acetonides. The application of this protocol to the synthesis
of nucleosides and carbohydrates is underway in our
laboratory and the results will be reported in the due
course.
(h)
(%)
O
O
O
AcO
AcO
O
RO
RO
O
O
O
O
a
b
c
1 R = H
3 R = Ts
5 R = Ac
6 R = Bz
2 R = Ac
4 R = Ts
2 R = Ac
7 R = Bz
2.5
2
1.5
1.5
89
83
90
88
d
O
O
AcO
AcO
O
O
e
f
1.5
88
91
92
O
O
O
O
O
9
8
OBz
O
O
O
O
O
O
AcO
AcO
O
1
OAc
11
10
HO
AcO
AcO
O
O
g
2
O
O
O
O
HO
O
O
9
12
AcO
AcO
O
HO
O
HO
HO
h
O
3
91
O
AcO
3. Experimental
13
2
a
Characterized by 1H NMR spectra.
Isolated yields.
All the conversion reaction were carried out at least
twice to ensure reproducibility.
b
3.1. Typical synthetic procedure
was the sole active function group. These results suggest
that this one-pot procedure could be applied to the syn-
thesis of 20-modified nucleosides and nucleotides.13
Bi(OTf)3ꢀxH2O (0.05 or 0.15 mmol) was added to a solu-
tion of substrate (1.0 mmol) and Ac2O (0.27 mL, 3.0 mmol)
in CH2Cl2 (5 mL), and stirred at rt (for the products listed
in Tables 1 and 2) or under reflux (for the products listed in
Table 3). After complete conversion, saturated aqueous
solution of NaHCO3 (10 mL) was added. The aqueous
solution was separated and extracted with CH2Cl2
(2 ꢁ 10 mL). The combined organic layers were washed
with brine (10 mL), dried (MgSO4) and concentrated under
reduced pressure. The residue was isolated through short
column chromatography on silica gel.
Under these reaction conditions, xylofuranose deriva-
tives 9, 20, 22 and 24 were also smoothly transformed into
the corresponding products 19, 21, 23 and 25 (Table 2,
entries a, c–e), respectively. Similar results (Table 2, entries
f–h) were also obtained as a number of anomeric
acetonides, such as 2, 4 and 7, which were treated with
Ac2O and Bi(OTf)3ꢀxH2O (5 mol %) in CH2Cl2 solution
at room temperature. The structures of the products
1
were all characterized with H NMR, 13C NMR and MS
Bi(OTf)3 (15 mol %)
AcO
AcO
O
AcO
AcO
O
AcO
AcO
O
OAc
OAc
AcO
Ac2O, CH2Cl2
reflux, 85%
O
AcO
OAc
AcO
O
O
OAc
2
26
29

Q.-P. Wu et al. / Tetrahedron Letters 49 (2008) 2714–2718
2717
Table 2
Unexpected products in the transformation of anomeric acetonides
Entry
Substrate
Producta
Time (h)
Yieldb (%)
R'O
R'O
O
O
OAc
OAc
O
R''O
R''O
O
O
a
b
c
d
e
9 R0 = R00 = Ac
19 R0 = R00 = Ac
16 R0 = R00 = Bz
21 R0 = Bz, R00 = p-Ts
23 R0O = H, R00 = Bz
25 R0 = R00 = Bn
3
2.5
2
2.5
0.5
91
91
92
88
83c
15 R0 = R00 = Bz
20 R0 = Bz, R00 = p-Ts
22 R0O = H, R00 = Bz
24 R0 = R00 = Bn
R'O
R''O
O
R'O
R''O
O
OAc
OAc
R'''O
R'''O
O
O
O
f
2 R0 = R00 = R000 = 0A00 c
26 R0 = R00 = R000 = 0A00 c
4.5
3.5
2.5
85
87
86
g
h
a
4 R0 = R00 = Ac, R = p-Ts
7 R0 = R00 = Ac, R000 = Bz
27 R0 = R00 = Ac, R = p-Ts
28 R0 = R00 = Ac, R000 = Bz
Characterized by 1H NMR, 13C NMR (ARX 400 MHz and 100 MHz) and MS spectra.
b
c
Isolated yields.
Bi(OTf)3ꢀxH2O (3 mol %).
Table 3
Direct transformation of anomeric acetonides into acetates
Entry
Substrate
Producta
Time (h)
Yieldb (%)
R'O
O
R'O
O
R''O
R''O
O
R'''O
OAc
R'''O
O
OAc
a
b
c
2 R0 = R00 = R000 = 0A00 c
29 R0 = R00 = R000 = 0A00 c
5
5.5
6.5
85
85
87
4 R0 = R00 = Ac, R = p-Ts
7 R0 = R00 = Ac, R000 = Bz
30 R0 = R00 = Ac, R = p-Ts
31 R0 = R00 = Ac, R000 = Bz
R'O
O
R'O
O
O
R''O
OAc
R''O
O
OAc
d
e
a
9 R0 = R00 = Ac
15 R0 = R00 = Bz
32 R0 = R00 = Ac
33 R0 = R00 = Bz
6.5
6
82
86
Characterized by 1H NMR spectra (ARX 400 MHz).
Isolated yields.
b
York; (c) Sartori, G.; Ballini, R.; Bigi, F.; Bosica, G.; Maggi, R.;
Righi, P. Chem. Rev. 2004, 104, 199–250.
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